Picking up one’s marbles and going home

One of the greatest gifts anyone can give is to donate his body to science after death. Such anatomic gifts contribute to the training of medical students, residents, and other medical professionals as well as being used for research that can contribute to the advancement of medical science. One of the things that makes an anatomic gift such a profound gift is that the donor usually has little control over what their body or body parts will be used for. There is, thus, more than a little trust in medical science involved in these gifts. When the deceased is a child, the donation of a child’s body or part of a child’s body to medical research is an even more amazingly generous gift. Such donations are precious gifts that are difficult enough to persuade people to give. It doesn’t take much to turn a “yes” answer into a “no.”

That’s why an article by Katie Wright at the anti-vaccine crank blog entitled Courchesne Brain Study Not Worth Sacrificing our Children Further really irritated me. Basically, Wright is saying that she used to think she would donate her child’s body to science if he were ever to die but, because she doesn’t like the result of a study that studied the brains of deceased autistic children and compared them to neurotypical controls, she’s now changed her mind:

If Christian’s deceased body could meaningfully contribute to innovative causation research, it would be very, very hard, but I would say yes and donate his body. If his brain were used to accelerate true progress I think it would be a great tribute to his spirit. I am sure most ASD parents feel the same way.

However the recent Courchesne Study made me change my mind about donating Christian’s brain to science. This study represents my nightmare, the worst-case scenario. Children’s brains have been used for politically driven poor quality science. I would rather Christian be buried with his brain intact than used for such abysmal research.

Why is the research so “abysmal”? Wright, who has no qualifications in science, proclaims it so because the results do not fit with her preconceived belief that vaccines cause autism and that her son Christian’s autism is due to “vaccine injury.” It is, in fact, a study that some of my readers sent to me when it first came out a couple of weeks ago. It just so happened to be around the time I was out of town giving a talk; so somehow it slipped through the cracks, as so many other worthy blogging topics often do because I just can’t blog about everything that is of interest to me. On the other hand, sometimes I’m given a chance to revisit one of these topics when someone like Katie Wright decides to go all full mental jacket on it.

This study was described in news articles that appeared around the time of its release, but, as always, I’ll go to the source, an article in JAMA entitled Neuron Number and Size in Prefrontal Cortex of Children With Autism. The study came out of UCSD and presents some provocative findings. It’s a preliminary study, given that it only examined the brains of 13 children, seven autistic boys and six control boys, but its results are fascinating and, best of all, hypothesis-generating. In brief, the authors obtained these brains from the National Institute of Child Health and Human Development (NICHD), University of Maryland Brain and Tissue Bank, the Autism Tissue Program at the Harvard Brain Tissue Resource Center, and the New York State Institute for Basic Research in Developmental Disabilities. As you might expect, young postmortem cases are scarce and difficult to come by for research, again, pointing to the importance of anatomical donations that Wright characterizes in this case as “sacrificing our children further” over.

Contrary to the way Wright portrays the study, which, if you believe her, was barely different from Young Frankenstein using the brain from Abby Normal, investigators were very careful to try to quantify the number of neurons in the prefrontal cortex (PFC) in both autistic and normal brains. The brains were analyzed by expert anatomists who were blinded to the group from which the brain came. The findings were simple:

Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, −8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children.

Leading the authors to conclude:

In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.

Again, this was a preliminary study with small numbers, which makes it even more surprising that a significant difference in neuronal counts was found. Considering normal variation among humans and the fact that, given the scarcity of postmortem tissue from children, it’s amazing that the investigators found anything at all. Could it be a spurious result? Sure. That’s why it needs to be confirmed with a bigger study; that is, if a bigger study can even be done. It’s also consistent with other lines of evidence implicating brain overgrowth in certain anatomic structures as being somehow related to the development of autism. What this tells us about the pathophysiology of autism remains to be seen, but it’s an intriguing observation that is likely to spur more research into the neurobiology of autism and autism spectrum disorders.

So what does Wright say about it? She doesn’t like it. Because it isn’t consistent with vaccines as a cause of autism (it being very difficult to imagine a mechanism by which vaccines could increase the number of neurons in such a manner, she’s very, very unhappy and assumes that it must be crap science:

What Couchesne’s study actually tells us is that 6 ASD children had more prefrontal cortex neurons than 7 typical children. There were no aged matched controls! 2 of the 7 “ASD” children did not even have an official ASD diagnosis! 5 of the 7 ASD kids were on anti-psychotic drugs. We have idea how these drugs affect developing brain tissue. 1 of the control children had been taking Concerta and klonopin. Another control had had an organ transplant and was on immunosuppressive drugs for lengthy periods of time. There are only 5 controls not, as far as we know, on various prescription drugs. The fact that this study was actually published only proves how low the bar is for ASD genetic and brain research. There are not enough hours this day to list all the incredible, innovative environmental research studies regularly rejected by autism research journals. A 7-person biomedical study would NEVER be published by JAMA, I promise you.

I’m not sure where Wright got the idea that two of the seven children didn’t have an ASD diagnosis. If I missed it somehow even though I read the whole paper and the online supplement, I’m sure someone will point out my mistake in the comments. The autistic cases were chosen primarily for having a diagnosis of autism, and in the text it reads:

No autism case had a diagnosis of Asperger syndrome or pervasive development disorder-not otherwise specified.

As for the rest of the obfuscation that Wright throws out about antipsychotic drugs is just that: Obfuscation. There is a table in the paper that lists all the cases and controls and describes a bit about their medical background; several of the autistic children were on psychotropic medications, which is not uncommon in children with autism. I rather suspect that when Wright wrote “We have idea how these drugs affect developing brain tissue” that she in fact meant “We have no idea how these drugs affect developing brain tissue.” Assuming that’s what she meant, she’s wrong, of course. We actually have a pretty good idea how many of these drugs affect developing brain tissue. At the very least, as the authors point out, none of these drugs are known to affect the number of neurons in the PFC. In essence, Wright’s complaints are all smoke and mirrors, whines designed to cast doubt on the study. In fact, the only points she makes that are semi-reasonable is that this was a small study (which the authors concede multiple times in the paper, pointing out that it is a preliminary study) and that maybe the criticism that including the child who had had cancer and a multiorgan transplant in the control group might not have been the best choice, given the chemotherapy treatment and immunosuppressive medications the child was on.

Not surprisingly, Wright doesn’t know what she’s talking about. It’s the perfect example of the Dunning-Kruger effect, the arrogance of ignorance, at work. It’s not as though the investigators in this study didn’t go to great lengths to try to control for the other confounding factors that she complains about, namely the lack of age-matched controls. Did she not pay attention to the part of the paper that points out how scarce postmortem brains from children that can be used for this sort of research are? Scientists make due with what they have. Wright is, in essence, intentionally making the perfect the enemy of the good and treating this study as though it were more than a preliminary study. She’s basically criticizing it because it is a preliminary study, even though, once again, the authors say right in the article that it’s a preliminary study.

Perhaps one of the most important implications of this study is mentioned in the discussion, and it’s obvious that this is the real reason Wright hates this study:

Also, prefrontal neuron counts in controls did not vary with age, which is concordant with literature that cortical neurons are generated prenatally, not postnatally.

Or, as this news report quotes Dr. Max Wiznitzer:

But since the excess neurons were found in a part of the brain that develops before a child is born, it points to a prenatal problem playing a role in autism.

“This is not consistent with that claims that heavy metals [from vaccines for example] cause the death of brain cells,” says Wiznitzer, because there are too many brain cells not less.

And that’s exactly why Wright is so upset. This study suggests that, whatever causes autism, it probably happens before birth, not after. If true, that rules out vaccines as a cause. Of course, we already have abundant scientific, clinical, and epidemiological evidence that fails to implicate vaccines as a cause of autism. It’s not as though scientists haven’t looked, either. Multiple large, well-designed studies have failed to find a correlation between vaccine and autism. As hypotheses go, the vaccine-autism hypothesis is as dead as dead can be, at least as dead as the famous parrot in a famous Monty Python sketch. Truly, it’s “pinin’ for the fjords.”

But, of course, to Wright, it’s all a huge conspiracy. Note how she writes that a study this small would never have been published in JAMA. Of course, the wag in me can’t help but note that this study is basically the same size as the infamous 1998 Lancet study published by Andrew Wakefield. One wonders whether Katie thinks that study should ever have been published in The Lancet, which is at least as high an impact a journal as JAMA. After all, the studies were basically the same size; so presumably she thinks that Wakefield’s study was no good either. But wait! I spoke too soon. Wright loves Andrew Wakefield because his “research” (such as it is) supports her pseudoscientific belief that vaccines cause autism. She even called the British General Medical Council investigation that led to Andrew Wakefield having his medical license stripped from him a “crime against humanity.” In other words, if a study with 12 or 13 subjects supports her belief that vaccines cause autism, she has no concern about the number of subjects, even when there is no control group.

I’ll take a moment to educate Wright why this study passed muster for JAMA and a study of “biomedical interventions” with only 13 subjects wouldn’t. It’s because it was incredibly difficult to obtain 13 suitable brains from children to study in this manner. Given the difficulties involved, this study was actually rather large. In the case of “biomedical” treatments, scientists would be looking at living children, meaning that there would be no barrier equivalent to what Courchesne et al faced in doing their study to recruiting a more statistically robust number of subjects.

Never mind that, though. According to Wright, this conspiracy is so pervasive that it prevents any scientist from doing anything other than gene-based research:

Families are frequenting told there isn’t enough research money available to address these issues. But guess what there is plenty of money for? Brain and gene research! These “Autism Centers for Excellence” centers blow almost $17 million a year on redundant brain and gene research. It is estimated that 50% of the ACE budgets go to overheard. There is no consumer oversight or public accountability for the money they spend. The NIH doles of autism research money behind closed dollars and without consumer input (they are under no obligation to follow the IACC recommendations), and guess what they love to fund the most? Brain and gene research.

Maybe, just maybe, the reason that the NIH funds brain and gene research is because that is the sort of research that is most likely to illuminate the biological mechanisms that lead to autism and thus point the way to treatments. The “biomedical” treatments that Wright is so enamored of are, by and large, pure quackery with no randomized clinical trial evidence to support their efficacy, much less even a modicum of biological plausibility.

Much like the notion that vaccines cause autism.

None of this stops commenters from dropping bombs of ignorance like:

The deceptive part of the report was the speculation that the increase in pre-frontal cortex neurons happened in utero. This could only be speculative and was probably intended to absolve post utero toxic exposures (e.g., mercury, which can cause abnormal cell growth in the CNS).

Uh, no. It’s not “speculation.” It’s a conclusion based on the known biology of brain development. The prefrontal cortex is already known to develop before birth. The authors even point out that the number of neurons in the prefrontal cortex was independent of age, consistent with completion of its development before birth. Seriously, these people need to learn a bit of neurobiology and actually think.

Even worse than the unrelenting ignorance on display in the article and in the comments, in the end Wright writes that “this Courchesne study has changed my mind” about donating her son’s brain to science. Because a single study doesn’t show what she wants it to show, she’s changed her mind. As if we’re supposed to be impressed. After all, fortunately the deaths of children are uncommon. Fortunately for both her and her son, it’s highly unlikely that wright will ever be called upon to donate her son’s brain to research, and that’s a good thing. No one wants to see a child die. Even though it’s an empty threat, though, Wright’s attitude is very much akin to that of a child who, if he doesn’t get her way, threatens to take all his marbles and go home. The study didn’t show what she wanted it to show; so Wright “changes her mind” about tissue donation. Even if the study to which she objects were crap, her reaction would be akin to tearing up your organ donation card because an alcoholic got a liver, after which he went back to drinking and destroyed the new liver or because Steve Jobs got a liver for a somewhat dicey indication to treat his cancer and his cancer recurred a year and a half later.

One can only hope that she doesn’t persuade other parents.